Epidemiology of rotaviral infection in adults

Although classic rotaviral gastroenteritis occurs in children between the ages of six and 24 months, infection with rotavirus is common in all age groups, including adults. Virtually all adults have been infected, as is demonstrated by the presence of serum antibodies, but previous infection does not protect against new infection with the same or a different serotype. Rotaviral infection of adults is seen in five settings: secondary contacts from pediatric cases, with variable attack rates in adults; waterborne outbreaks, which are often characterized by higher attack rates in adults than in children; travelers' diarrhea; epidemic spread in isolated or closed populations, often in the absence of contact with children; and endemic infections, which may account for 5%-10% of sporadic cases of diarrhea in adults. Frequent asymptomatic infections with rotavirus occur, and they may be important in the epidemiology of the disease. Although rotaviral infections in adults tend to be milder than those in children, death due to rotaviral infection in adults have been reported.     

Molecular Epidemiology of Norovirus (NoV) Infection in Mie Prefecture: The Kinetics of Norovirus Antigenemia in Pediatric Patients

Few studies have shown the presence of norovirus (NoV) RNA in blood circulation but there is no data on norovirus antigenemia. We examined both antigenemia and RNAemia from the sera of children with NoV infections and studied whether norovirus antigenemia is correlated with the levels of norovirus-specific antibodies and clinical severity of gastroenteritis. Both stool and serum samples were collected from 63 children admitted to Mie National Hospital with acute NoV gastroenteritis. Norovirus antigen and RNA were detected in sera by ELISA and real-time RT-PCR, respectively. NoV antigenemia was found in 54.8% (34/62) and RNAemia in 14.3% (9/63) of sera samples. Antigenemia was more common in the younger age group (0–2 years) than in the older age groups, and most patients were male. There was no correlation between stool viral load and norovirus antigen (NoV-Ag) levels (r_s = −0.063; Cl −0.3150 to 0.1967; p = 0.6251). Higher levels of acute norovirus-specific IgG serum antibodies resulted in a lower antigenemia OD value (n = 61; r = −0.4258; CI −0.62 to −0.19; p = 0.0006). Norovirus antigenemia occurred more commonly in children under 2 years of age with NoV-associated acute gastroenteritis. The occurrence of antigenemia was not correlated with stool viral load or disease severity.     

Rotavirus antigenemia in patients with acute gastroenteritis

Although rotavirus infections are generally considered to be confined to the intestine, recent reports suggest that extraintestinal disease occurs. We studied whether rotavirus infection was associated with antigenemia during a major outbreak of gastroenteritis in the Kingston metropolitan area, during July-August 2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples (including from 2 deceased individuals) but in only 1 of 53 control samples. Serum antigen levels were inversely associated with time since symptom onset and were directly associated with antigen levels in stool (P = .02). Serum antigen levels were significantly elevated during primary infections (acute-phase serum immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections (acute-phase serum IgG titers, > or = 25) (P = .02). Antigenemia was common in this outbreak and might provide a mechanism to help explain rare but well-documented reports of findings of extraintestinal rotavirus. In situations in which stool samples are not readily available (i.e., patients with severe dehydration or those recently recovered or deceased), serum testing by enzyme immunoassay offers a new and practical diagnostic tool.     

Treatment of rotaviral gastroenteritis with Qiwei Baizhu powder

AIM To observe the effects of Qiwei Baizhu Powder(QWBZP)on rotaviral gastroenteritis in children and inanimal models.METHODS Enrolled patients were divided into twogroups,and one group was treated with oral rehydrationsolution(ORS)and the other treated with oral liquid ofQWBZP.Neonate mice were orally infected with 50μLrotavirus suspension(4×10~8 PFU/mL)and treated withORS or oral liquid of QWBZP,respectively.RESULTS Eighty-three cases of rotaviral gastroenteritistreated with QWBZP revealed a better efficacy than thattreated with ORS(X~2=10.87,P<0.05).The contents ofsodium and glucose as well as number of patients withpositive human rotavirus antigen in stool in QWBZP groupwere all less than that in ORS group.In animal models,QWBZP was found effective in treating rotavirusgastroenteritis in neonate NIH mice,as compared withcontrol groups.In QWBZP group,the mortality of infectedmice was decreased by 73.3%,the body weight ofinfected mice was increased,the contents of sodium andglucose as well as number of mice with positive rotavirusantigen in feces were significantly reduced,and thepathological changes such as damage of small intestinalmucosa and villi were also obviously alleviated.CONCLUSION QWBZP has effects on improving theabsorptive function of small intestine,shortening theduration of diarrhea and rotavirus shedding from stool andalleviating the pathological changes of small intestineinduced by rotavirus.     

Rotavirus carriage, asymptomatic infection, and disease in the first two years of life. II. Serological response

Serological response to rotavirus and virus shedding were prospectively studied in 179 children (neonatal to 24-month-old) upon admission to a hospital during an 11-month period. Analysis of the evolution of IgG and IgM ELISA titers revealed 24 cases of rotaviral disease (serological response and diarrhea), 13 cases of asymptomatic infection (serological response and no diarrhea), 36 cases of virus carriage (absence of a serological response), three cases of past infection, and six possible cases of nosocomial infection. Rotaviral disease was encountered two out of three times and was characterized by diarrhea associated with fever and vomiting. Asymptomatic rotaviral infection and disease, observed from the neonatal period onwards, affected 2% of neonates, 20% of one- to six-month-old children, and 37% of 7-24-month-old children. In contrast, virus carriage occurred in 27%, 19%, and 14% of those children respectively. Altogether these results indicate that during the period 1-24 months of age, when asymptomatic rotaviral infection and disease were prevalent, approximately two of 10 children had rotaviral disease, one of 10 had asymptomatic infection, two of 10 were virus carriers, and five of 10 were not infected with rotavirus.     

Treatment of rotaviral gastroenteritis with Oiwei Baizhu powder

AIM To observe the effects of Qiwei Baizhu Powder ( QWBZP) on rotaviral gastroenteritis in children and in animal models.``METHODS Enrolled patients were divided into two groups, and one group was treated with oral rehydration solution(ORS) and the other treated with oral liquid of QWBZP. Neonate mice were orally infected with 50 μLrotavirus suspension (4 × l0s PFU/mL) and treated with ORS or oral liquid of QWBZP, respectively.``RESULTS Eighty-three cases of rotaviral gastroenteritis treated with QWBZP revealed a better efficacy than that treated with ORS (x2 - 10.8T, P<0.05). The contents of sodium and glucose as well as number of patients with positive human rotavirus antigen in stool in QWBZP group were all less than that in ORS group. In animal models,QWBZP was found effective in treating rotavirus gastroenteritis in neonate NIH mice, as compared with control groups. In QWBZP group, the mortality of infected mice was decreased by 73.3%, the body weight of infected mice was increased, the contents of sodium and glucose as well as number of mice with positive rotavirus antigen in feces were significantly reduced, and the pathological changes such as damage of small intestinal mucosa and villi were also obviously alleviated.``CONCLUSION QWBZP has effects on improving the absorptive function of small intestine, shortening the duration of diarrhea and rotavirus shedding from stool and alleviating the pathological changes of small intestine induced by rotavirus.``     

Parasite antigenemia in untreated and treated lymphatic filarial infections

To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment.     

Rotavirus-specific antibody response in saliva of infants with rotavirus diarrhea

The reliability of saliva as an indicator of rotavirus infection was assessed among 15 infants (3-12 months) with rotaviral and 15 with nonrotaviral diarrhea. Paired salivary samples collected during acute and convalescent phases were tested for rotavirus-specific IgA and IgM by an ELISA. The sensitivity of IgA or IgM alone to predict infection was 53.3% and 46.6%, respectively; used in conjunction, the sensitivity rose to 80%. It seems that infants with rotaviral diarrhea mount mucosal antibody responses as reflected in their saliva; possibly salivary antibodies could be used to evaluate vaccine "take" in rotavirus vaccine trials.     

Serologic correlates of protection against enterotoxigenic Escherichia coli diarrhea

BACKGROUND: We conducted a nested case-control study in 397 rural Egyptian children <36 months of age to assess the correlation between serum levels of antibodies against toxin and colonization factors (CFs) and the risk of homologous enterotoxigenic Escherichia coli (ETEC) diarrhea. METHODS: Active case detection was performed via semiweekly home visits, and blood was obtained at 3-month intervals. After each serosurvey, case subjects were selected from children experiencing a CF antigen (CFA)/I-, CFA/II-, CFA/IV-, or heat-labile enterotoxin (LT)-ETEC diarrheal episode during the subsequent 3 months. Up to 5 control subjects per case subject were selected from children who did not experience an ETEC diarrheal episode during the corresponding interval. Serum titers of immunoglobulin G antibodies against CFA/I, coli surface antigen (CS) 3, CS6, and LT were measured by enzyme-linked immunosorbant assay. RESULTS: The distribution of serum titers of LT, CS3, and CS6 antibodies did not differ between the case and control subjects. For children <18 months of age, serum titers of CFA/I antibody were inversely related to the risk of CFA/I-ETEC diarrhea; reciprocal serum titers of CFA/I antibody > or =76 were associated with a 77% reduction in the odds of CFA/I-ETEC diarrhea. CONCLUSION: Induction of reciprocal serum titers of antibodies against CFA/I within or above the 76-186 range should be further evaluated as a predictor for assessment of the ability of candidate vaccines to protect against CFA/I-ETEC diarrhea.     

Gastric emptying of liquid in children suffering from acute rotaviral gastroenteritis.

Nausea and vomiting commonly occur in children suffering from rotaviral diarrhoea. Gastric emptying was studied in 10 children (age six to 12 months) suffering from acute diarrhoea caused by rotavirus using a dye dilution double sampling technique. The test meal was 5% dextrose in water and this test was repeated 12 weeks after recovery. The median (range) of the percentages of the liquid meal remaining in the stomach at 5, 10, 20, 40, and 60 minutes after instillation of the meal were 82 (79-90), 70 (61-86), 51 (38-76), 26 (14-53), and 13 (2-35) respectively in the acute stage, whereas after the recovery period the values were 76 (70-79), 58 (49-63), 33 (24-40), 11 (2-26), and 3 (0-7). The differences were statistically significant. The half time of gastric emptying (t1/2) was 19.5 (14-30) minutes in acute stage, and 13.1 (10-15) minutes during follow up (p less than 0.01). Rotaviral gastroenteritis is accompanied by abnormal gastric motor function, as manifested by delayed emptying of a liquid meal.     

Analysis of rotavirus antigenemia in hematopoietic stem cell transplant recipients

Systemic rotavirus infection, such as rotavirus antigenemia, has been found in immunocompetent rotavirus gastroenteritis patients. However, the pathogenesis of rotavirus infection in immunocompromised transplant recipients remains unclear. Enzyme-linked immunosorbent assay was used to measure rotavirus antigen levels in serially collected serum samples obtained from 62 pediatric patients receiving allogeneic hematopoietic stem cell transplants (HSCT). Rotavirus antigen was detected in 43 (6.8%) of 633 serum samples (8 of 62 patients). The duration of rotavirus antigenemia ranged between 1 and 10 weeks, and diarrhea was concurrent with rotavirus antigenemia in Cases 3, 6, 7, and 8. The level of viral antigen in the transplant recipients (0.19 ± 0.20) was significantly lower than that observed in serum samples collected from immunocompetent patients on either day 1 (0.49 ± 0.18, P = 0.0011) or day 3 (0.63 ± 0.09, P = 0.0005). A patient who received a graft from a human leukocyte antigen (HLA)-mismatched donor was at significant risk for rotavirus antigenemia (P = 0.024; odds ratio = 9.44) in comparison to patients who received grafts from HLA-matched donors. Although the duration of antigenemia was clearly longer in HSCT patients than in immunocompetent rotavirus gastroenteritis patients, the levels of viral antigen were not as high. Therefore, mismatched HLA may be a risk factor for rotavirus antigenemia after HSCT.     

Demonstration of antigenemia by radioimmunoassay in rabbits experimentally infected with Aspergillus.

Antigens were detected in the blood of rabbits infected with Aspergillus fumigatus by a solid-phase (tube) radioimmunoassay (RIA). The radiolabel for the assay was a polysaccharide-rich alkali extract (APAE) from the mycelia of A. fumigatus. Before this extract could be suitable labeled with 125I, it had to be conjugated with tyramine. Rabbits immunized with heat-killed mycelia had titers of antibody in serum of as high as 1:38,000 against this radiolabeled antigen. With unlabeled and unconjugated APAE as the standard antigen, the sensitivity of the RIA was 12 ng per test, or 500 ng/ml. Antigenemia was detectable by RIA three days after infection of rabbits with A. fumigatus. Blood cultures taken concomitantly were uniformly negative. These results indicate that antigenemia occurs in invasive aspergillus infection and in such cases can be detected by RIA. These observations may be important in the diagnosis of invasive aspergillus infections in humans.     

Pneumococcal pneumonia: capsular polysaccharide antigenemia and antibody responses.

Capsular polysaccharide was detected in the serum in 19 of 46 patients with pneumococcal pneumonia. Antigenemia was strongly associated with bacteremia and with infection by low-numbered serotypes. During antibiotic therapy, the concentration of polysaccharide in the circulation declined progressively, but circulating antigen remained detectable in two thirds of cases for 2 weeks or longer. The development of measurable type-specific antibody was delayed in patients with antigenemia. It is not known whether this delay was due to diminished antibody production or to neutralization of antibody by circulating antigen. Despite effective antibiotic therapy many patients with antigenemia had a severe and protracted illness; this may have been related to diminished availability of antibody early in the infection.     

Sequential cytomegalovirus antigenemia monitoring in kidney transplant patients treated with antilymphocyte antibodies

BACKGROUND: Antilymphocyte antibodies (ALA) use is related to disseminated cytomegalovirus (CMV) disease after kidney transplantation. Strict surveillance of CMV infection, preemptive antiviral treatment or concomitant ganciclovir and ALA use are proposed as an attempt to prevent related clinical complications. Our objective was to describe the pattern of CMV infection, based on sequential antigenemia detection, after ALA treatment. PATIENTS AND METHODS: Thirty renal transplant patients were prospectively screened for CMV infection after ALA treatment. CMV antigenemia (pp65 antigen detection) was monitored twice a week in the first month and weekly until 60 days after the beginning of ALA therapy. Any positive value of antigenemia was considered CMV infection. RESULTS: Twenty-eight (93.3%) patients were CMV positive (IgG) before transplantation. The mean duration of ALA treatment was 12.1+/-2.4 days. Positive antigenemia was detected in 24 (80%) patients, a mean of 52.5+/-15 days after transplant and 44.7+/-14 days after the beginning of ALA treatment. The median antigenemia count was 7 positive cells/300,000 neutrophils (range: 1-227). Antigenemia preceded clinical symptoms by 5.8 days (0-28 days). Eighteen (75%) of 24 positive patients received ganciclovir treatment: 8 patients (26.7%) for viral syndrome, 2 patients (33.3%) for invasive disease, and 8 patients (26.7%) as part of preemptive therapy, asymptomatic with high antigenemia values. Six pp65-positive patients with low counts were followed up until a negative result and remained asymptomatic without any specific treatment. CONCLUSION: CMV infection was frequent after ALA treatment in this group and generally occurred late after completion of treatment. Antigenemia was a reliable tool to guide preemptive treatment in these patients, and such strategy is an alternative option compared to the prophylactic use of ganciclovir with ALA treatment.     

Rotavirus carriage, asymptomatic infection, and disease in the first two years of life. I. Virus shedding

From September 1979 to July 1980 inclusive, rotaviruses were prospectively detected by electron microscopy (EM) and ELISA in 82 (29%) of 283 children under two years of age who were admitted to a general pediatric ward in Paris. Rotavirus was found in 43 (36%) of 119 children with diarrhea and in 40 (24%) of 164 children without diarrhea; thus of 83 children shedding rotavirus, 40 (48%) were not diarrheic. Virus shedding that was not associated with diarrhea was observed in 71% of neonates, in 50% of one- to six-month-old children, and in 26% of 7-24-month-old children. Rotavirus shedding was statistically correlated (P less than .01) only with those cases of diarrhea with fever and vomiting ( DFV syndrome). Consequently, relative risk (RR) for the DFV syndrome in patients who were shedding virus was 2.07 (P less than .001) vs. 0.95 for other types of diarrhea. These observations show that asymptomatic rotaviral infection is not an infrequent occurrence; that the association between rotavirus and diarrhea is not necessarily an etiologic one; and that the DFV syndrome appears as a major clinical expression of rotaviral disease. Consequently, recovery of rotavirus from feces is of little diagnostic significance since it does not give a differentiation between rotavirus-induced and rotavirus-associated diarrhea.     

Epidemiology and burden of rotavirus diarrhea in Thailand: results of sentinel surveillance

Diarrhea remains an important cause of morbidity and mortality among children in Thailand, with >1 million cases reported in 2002. In anticipation of the development of vaccines against rotavirus, we evaluated the disease burden associated with rotavirus infection in Thai children and evaluated the rotavirus serotypes now circulating in Thailand. Diarrhea surveillance was conducted at 6 Thai hospitals in different geographic areas. Community-based surveillance was conducted in Huaykrajao District, Kanchanaburi Province. During the 24 months of surveillance, 4057 children were admitted to the 6 participating hospitals, and 1950 stool samples were collected. Of these stool samples, 43% (838) were positive for rotavirus. All rotavirus-positive stool samples were evaluated to identify their serotypes; 54.8% of samples were of serotype G9, which was predominant each year. Other identified rotavirus serotypes included G2, G4, G1, and G3 (17.2%, 5.3%, 0.8%, and 0.1% of isolates, respectively). Approximately one-half of the children hospitalized with rotavirus diarrhea were <1 year old. Community surveillance showed the proportion of cases of rotavirus diarrhea in the community to be much lower than that in the hospitalized population (12.2% vs. 43.0%).     

Circulating schistosomal antigen in diagnosis and assessment of cure in individuals infected with Schistosoma mansoni.

The effectiveness of praziquantel in treating schistosomiasis is most commonly assessed by quantitating egg production or anti-schistosome antibodies in serum. We have used a monoclonal antibody (MAb)-based antigen-capture enzyme-linked immunosorbent assay (ELISA) for the serologic diagnosis of schistosomiasis, and to monitor the efficacy of praziquantel therapy in 49 individuals with parasitologically proven schistosomiasis. The MAb used, 128C3/3/21, recognizes a repeating carbohydrate epitope expressed at all stages of parasite development, and antibodies recognizing this epitope are found in the serum of infected humans. The overall sensitivity of the ELISA was 78%, with a sensitivity of 100% for patients excreting greater than 100 eggs/g of feces and 72% for those excreting less than 100 eggs/g of feces. The positivity of the ELISA was directly related to the fecal egg counts obtained on days -3, -2, and -1 before treatment with praziquantel, but there was no correlation between antigen levels and the clinical stage of the disease. After praziquantel treatment, we observed a highly significant correlation (P less than 0.0001) between the time elapsed since treatment and the decrease in antigenemia. Furthermore, although no eggs were detected in any of the stool specimens at week 12 after treatment, the antigen was detected in 21% of the treated patients (seven of 33 ELISA-positive patients). Antigen levels decreased over the 12-week period in six of these patients, whereas the antigen level increased with time in one individual. The persistence of antigenemia suggests that these individuals are either still clearing antigen or remain infected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ecologic and biologic determinants of filarial antigenemia in bancroftian filariasis in Papua New Guinea

The relationship between filarial antigenemia and lymphatic pathology was investigated in residents of 11 villages in an area of Papua New Guinea where Wuchereria bancrofti is endemic. Antigenemia was determined in 1322 persons by means of the Og4C3 antibody capture assay. Prevalence of antigenemia by village ranged from 61.7% to 98.2% and did not vary by sex. Antigen level increased with transmission potential among the 4 villages with measured transmission potential (r(2)=.945; P=.028). Antigenemia was associated positively with age in villages with the lowest annual transmission potentials (45 and 404 infective larvae/year; P<.001), but was distributed evenly across age groups in villages with increased transmission (1485 and 2518 infective larvae/year). These data suggest that children and adults have similar worm burdens in areas of high transmission, whereas worm burdens in areas of lower transmission increase with age. These results may be useful in the design and evaluation of programs aimed at eliminating lymphatic filariasis.     

Intestinal protein loss in acute and persistent diarrhea of early childhood

GOALS: To determine fecal protein loss in children with acute and persistent diarrhea. BACKGROUND: In children with diarrhea, ongoing losses of endogenous proteins have been suggested as contributing to impairment of nutritional and immunologic status. However, there is a paucity of information and inconclusive data in the literature. STUDY: Fecal protein loss was assessed prospectively in children (<3 years of age) with acute diarrhea (<7 days' duration) or persistent diarrhea (>14 days) and in controls using alpha-1-antitrypsin determination; fecal protein loss then was correlated with age, duration of diarrhea, nutritional status, plasma proteins, and stool pathogens. RESULTS: Children with acute diarrhea (n = 43) and those with persistent diarrhea (n = 41) had significantly higher fecal alpha-1-antitrypsin levels compared with controls (n = 14) (2.26 +/- 1.71 and 2.25 +/- 1.51, respectively, vs. 1.02 +/- 0.73 mg/g stools; p = 0.002). However, there was no significant decrease of plasma albumin, globulin, or immunoglobulins. Fecal protein loss did not differ significantly among stool pathogens (bacterial, viral, and parasitic) and demonstrated no significant correlation with age, duration of diarrhea, or nutritional status (mild malnutrition). CONCLUSIONS: Enhanced fecal protein loss was observed in more than 50% of children with acute and persistent diarrhea caused by various pathogens. This did not correlate with age, duration of diarrhea, or nutritional status and did not result in significant decrease of plasma proteins or immunoglobulins. This protein-losing enteropathy does not appear to have a causal role in perpetuation of diarrheal episodes in children with mild malnutrition.     

Circulating staphylococcal antigen in humans and immune rabbits with endocarditis due to Staphylococcus aureus: inhibition of detection by preexisting antibodies.

A radioimmunoassay for staphylococcal antigen that had detected antigenemia in each of 12 nonimmune rabbits with staphylococcal endocarditis detected antigen in sera from one of nine humans and two of eight immune rabbits with Staphylococcus aureus endocarditis. Staphylococcal antigens could be detected at concentrations as low as 0.78 microgram/ml when diluted in normal rabbit serum, compared with 6.25 microgram/ml when diluted in normal human serum and greater than 25 microgram/ml when diluted in immune rabbit or human serum. Low titers of staphylococcal antibody were found in normal rabbit serum compared with immune rabbit and normal or immune human sera. Detection of staphylococcal antigen was inhibited when the antigen was diluted in the IgG and IgM fractions, but not in the albumin fraction, of normal human serum. This study demonstrated that antigenemia can be detected infrequently in patients and immune rabbits with staphylococcal endocarditis; staphylococcal antibodies inhibit detection of antigen, presumably through formation of immune complexes.